Fremanezumab, sold under the brand name Ajovy, is a medication used to prevent

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

s in adults. It is given by

injection under the skin Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, col ...

. The most common side effect is pain and redness at the site of injection. Other side effects include allergic reactions. It is in the

calcitonin gene-related peptide antagonist Calcitonin gene-related peptide (CGRP) receptor antagonists are a class of drugs that act as antagonists of the calcitonin gene-related peptide receptor (CGRPR). Several monoclonal antibodies which binds to the CGRP receptor or peptide have been ...

class of medications. It was approved for medical use in the United States in 2018, the European Union in 2019 and the UK in 2020.

Medical uses

Fremanezumab was shown to be effective in adults with four or more attacks per month.

Adverse effects

The most common adverse effects are reactions at the injection site, which occurred in 43 to 45% of people in studies (as compared to 38% under

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

Hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...

reactions occurred in fewer than 1% of patients.

Interactions

Fremanezumab does not interact with other antimigraine drugs such as

triptan Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, th ...

ergot alkaloid Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of thes ...

s and analgesics. It is expected to generally have a low potential for interactions because it is not metabolized by

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzymes.

Pharmacology

Mechanism of action

Fremanezumab is a fully humanized

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

directed against

calcitonin gene-related peptide Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 ( intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produ ...

s (CGRP) alpha and beta. The precise mechanism of action is unknown. It can be given with a quarterly interval.

Pharmacokinetics

After

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...

, fremanezumab has a

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of 55–66%. Highest concentrations in the body are reached after five to seven days. Like other proteins, the substance is degraded by

proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

to small

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s and

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s, which are reused or excreted via the kidney. The

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

is estimated to be 30 to 31 days.

History

Fremanezumab was discovered and developed by Rinat Neuroscience, was acquired by

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

in 2006, and was then licensed to Teva. It was approved by the

US Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

in September 2018. In March 2019, fremanezumab was approved for marketing and use in the European Union. The drug has been and is still being evaluated for diseases other than migraine, where the endogenous substance CGRP has been implicated in the pathology. Teva is still developing it for episodic

cluster headache Cluster headache (CH) is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s). There is often accompanying eye watering, nasal congestion, or swelling around the eye on the a ...

but stopped development of fremanezumab for the treatment of chronic cluster headache in 2018 after the primary endpoint of a Phase III trial was not met.

Chemistry

Fremanezumab is a humanized monoclonal antibody. It is produced using

recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...

Chinese hamster ovary cell Chinese hamster ovary (CHO) cells are an epithelial cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therapeutic proteins. They have foun ...

References

External links

* {{Portal bar , Medicine Antimigraine drugs Monoclonal antibodies